tbuckley/cabot-search huggingface dataset:
Association of polypharmacy and potential drug-drug interactions with adverse outcomes in older adults with advanced cancer receiving systemic treatment.
Authors: Mostafa Refaat Mohamed, Supriya Gupta Mohile, Katherine Juba, Hala Awad, Megan Wells, Kah Poh Loh, Marie Anne Flannery, Eva Culakova, Rachael Tylock, Nisarg Desai, Thomas Paul Bradley, Adedayo A. Onitilo, Erika E. Ramsdale
Journal: Journal of Clinical Oncology (2022)

12053 Background: Polypharmacy (PP) is common in older adults starting cancer treatment and associated with increased risk of potential drug-drug interactions (PDI). PP and PDI may affect treatment-related outcomes in older patients. This study evaluates the association of PP and PDI with systemic treatment adverse outcomes in older adults with advanced cancer. Methods: This secondary analysis of prospectively collected data from the GAP 70+ Trial (NCT02054741; PI: Mohile) enrolled patients aged 70+ with advanced (i.e. incurable) cancer; had ≥1 geriatric assessment domain impairment; and planned to start a new chemotherapy regimen or another regimen with high risk of toxicity. PP was assessed prior to initiation of treatment and defined as concurrent use of ≥8 medications (meds). PDI among all drugs were reviewed prior to initiation of treatment using Lexi-Interact ® Online with category D and X considered “major PDI”. Study outcomes were assessed within 3 months of treatment initiation and included: 1) total number of Grade ≥2 toxicities according to National Cancer Institute Common Toxicity Criteria; 2) total number of Grade ≥3 toxicities; and 3) early treatment discontinuation due to toxicity. Multivariable linear and logistic regression models were used to examine the association of PP and PDI with treatment adverse-outcomes adjusted for age, gender, cancer type, comorbidity, physical function, social support, and study arm. Results: Among 718 participants, the mean age was 77 (range 70-96); 43% were females; and 57% had lung or gastrointestinal cancers. The median number of meds was 5 (range 0-24); 28% received ≥8 concurrent meds; and 25% had ≥1 major PDI. The mean number of Grade ≥2 toxicities for patients with PP was 9.8 versus 7.7 in patients without PP (adjusted β=1.87, standard error [SE]=0.71, P&lt;0.01). The mean number of Grade ≥3 toxicities for patients with PP was 2.9 versus 2.2 in patients without PP (adjusted β=0.59, SE=0.29, P=0.04). Patients with ≥1 major PDI had 59% higher odds of early treatment discontinuation versus those without major PDI (adjusted odds ratio 1.59, 95% confidence interval=1.03-2.46, P=0.03). There was no significant association between PP and early treatment discontinuation. Major PDI were not significantly associated with toxicity (Ps&gt;0.05). Conclusions: In a cohort of vulnerable older adults with advanced cancer, PP and PDI are associated with increased risk of systemic treatment adverse outcomes. Providing meaningful screening and interventional tools to optimize medication use may improve treatment outcomes in these patients. Funding:UG1CA18996, U01CA233167.
Survey of Uruguayan women on knowledge related to the prevention of breast cancer.
Authors: Natalia Camejo, Cecilia Castillo, Dahiana Amarillo, Moira Bernate, Florencia Burguez, Eliana Darino, Adrian Deleon, Tatiana Milwa, Maria Barcia, Gabriel David Krygier
Journal: Journal of Clinical Oncology (2022)

e22504 Background: In Uruguay, breast cancer has the highest incidence and mortality of all cancer in women. Methods: To assess the knowledge of Uruguayan women about breast cancer screening for the early detection of BC. Material and Methods: This is a descriptive and observational study. A survey was applied to womwn, it was disseminated through social networks. Informed consent was requested at the beginning of the survey as an exclusive requirement to be able to carry it out. In the statistical analysis, the anonymity of the patients was maintained and the approval of the Ethics Committee of the Hospital de Clínicas was obtained. Results: 1859 women participated. 75.1% (1396) of those surveyed recognize BC as the one with the highest mortality in women. 52% (967) believe that 3 out of 10 women are at risk of developing BC, and 18.4% (342) do not know its prevalence. 60.2% (1119) recognize mammography as a test that has managed to reduce mortality from BC. 64.2% (1193) believe that it is done after 40 years of age. Regarding the frequency, 60.5% (1125) consider that it is carried out annually. The most considered risk factors for developing BC were smoking (60.9%, 1132), obesity (57%, 1.060) and sedentary lifestyle (56.8%, 1056). Conclusions: Our results show that the respondents are adequately informed about the importance of CM and the performance of screening mammography.
Prostate-specific membrane antigen PET response associates with radiographic progression-free survival following stereotactic ablative radiation therapy in oligometastatic castration-sensitive prostate cancer.
Authors: Philip Sutera, Matthew Deek, Ozan Cem Guler, Pervin Hurmuz, Mehmet Reyhan, Steven P. Rowe, William Hrinivich, Lei Ren, Ana Ponce Kiess, Daniel Y. Song, Ezgi Oymak, Kenneth J. Pienta, Martin Pomper, Felix Y Feng, Gokhan Ozyigit, Phuoc T. Tran, Ryan Phillips, Huseyin Cem Onal
Journal: Journal of Clinical Oncology (2022)

5011 Background: Emerging data suggest metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET/CT) can detect occult metastatic disease and has been proposed as a biomarker for treatment response. Herein we identify and validate a PSMA-PET biomarker for clinical outcomes following MDT in omCSPC. Methods: This was an international multi-institutional retrospective study of two completely independent cohorts of men with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation therapy (SABR) who underwent PSMA-PET/CT prior to and 3-6 months after treatment. Pre- and post-SABR PSMA-PET/CT standardized uptake value (SUV) was measured for all lesions and PSMA response defined discretely using a cutpoint of ≥ 30% decrease in SUV max . PSMA-PET response was correlated with lesion local control (LLC), radiographic progression-free survival (rPFS) defined using conventional and PET imaging, and metastasis-free survival (MFS) defined by conventional imaging alone. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with median follow-up of 29 months (IQR 18.5-41.3). Following SABR, 78.4% of lesions experienced a partial or complete PSMA response. Multivariable analysis demonstrated SUV response significantly associated with improved LLC (HR = 9.97, 95%CI 3.92-25.4; p &lt; 0.01). Patients with PSMA response in all lesions experienced significantly better rPFS (HR = 0.49, 95%CI 0.26-0.92; p = 0.03) compared to their counterparts and this maintained significance within both the discovery (p &lt; 0.01) and validation (p = 0.01) cohorts. Within the discovery cohort, patients with PSMA response in all lesions also experienced significantly improved MFS (HR = 0.24, 95%CI 0.07-0.85; p = 0.03); analysis of the independent validation cohort is ongoing. Conclusions: Following SABR, PSMA-PET response is a robust and externally validated radiographic biomarker for rPFS and appears to be associated with MFS pending validation. This approach holds promise for guiding clinical management of omCSPC.
A digital imaging analysis (DIA) platform for identifying tertiary lymphoid structures (TLS) in lung adenocarcinoma (LUAD).
Authors: Vladimir Kushnarev, Anna Belozerova, Daniil Dymov, Yuriy Popov, Nadezhda Lukashevich, Ivan Valiev, Diana Shamsutdinova, Aida Akaeva, Ilia Galkin, Lev Popyvanov, Viktor Svekolkin, Krystle Nomie, Anna Love, Alexander Bagaev, Ekaterina Postovalova, Nathan Fowler
Journal: Journal of Clinical Oncology (2022)

3142 Background: Previous studies of non-small cell lung cancer (NSCLC) have shown that TLS can be predictive of therapy response and a positive prognostic factor for survival. Currently, TLS identification is manually performed by pathologists with limited morphological criteria. Standardizing TLS detection with an automated DIA workflow could guide clinical trials in precision medicine by improving patient stratification. Here, we investigate the reproducibility and sensitivity of our DIA platform for evaluating TLS in LUAD using digital histopathology and machine learning. Methods: TLS were assessed by 3 pathologists on whole slide images (WSI) in a validation cohort of 22 LUAD samples using current TLS characterization criteria of dense lymphoid structures, the presence/absence of a germinal center, and high endothelial venules (HEVs). The intraclass correlation coefficient (ICC) was used to measure reproducibility between pathologists. The BostonGene DIA platform was used to train models for automated TLS detection. Quantitative measurements of area, lymphocyte number, and density of each TLS were obtained. A prospective cohort of 8 samples was used to compare pathologist and DIA identification of TLS. Normalized numbers of TLS in the tumor area were used for cohort stratification for overall survival (OS) analysis using the Kaplan-Meier method in an independent clinical cohort of 104 TCGA-LUAD patients. Results: A panel of 3 pathologists identified 326 unique TLS from 22 samples. Between-pathologist detection of TLS, independent of germinal center or HEV criteria, resulted in good reproducibility with an ICC of 0.77. Our DIA platform exhibited excellent reproducibility with an ICC of 0.94 when compared to validated prospective cohort annotation. In total, 155 and 189 TLS were identified by pathologists and our DIA platform, respectively. The DIA platform demonstrated a markedly improved sensitivity of 0.91 for TLS identification. Furthermore, OS analysis revealed that a TLS density greater than 0.94 TLS per mm 2 of tumor assessed by DIA is a statistically significant independent biomarker of better OS in the LUAD cohort from TCGA. Conclusions: These results demonstrate the BostonGene DIA platform detects TLS in LUAD, with improved reproducibility and sensitivity over previous methods. Additionally, the DIA platform showed a TLS density greater than 0.94 TLS per mm 2 of tumor is a positive prognostic marker for OS in LUAD. Standardized TLS DIA identification can be exploited in digital pathology applications for future clinical trials, informing clinicians of predictive and prognostic information during the decision-making process.
Trading satisfaction for experience: Development of an oncology patient experience survey.
Authors: Rachel Gorham, Rebekkah Schear, Robin Richardson, Elizabeth Ann Kvale
Journal: Journal of Clinical Oncology (2022)

e18667 Background: Patient-Reported Experience Measures (PREMs) are gaining favor over standard patient satisfaction surveys, providing a multidimensional approach to understand unique patients’ care experiences. However, while existing tools undergo robust creation and validation processes, many of these processes do not include input from patients themselves. The purpose of the present work was to describe the development of a patient experience survey to be distributed to oncology patients in an interdisciplinary care center, combining validated measures, site-specific considerations, and patient input. Methods: This questionnaire was designed through an iterative process over the course of 6 months. First, a focus group was conducted with advocates from our Patient Advisory Board to identify measures that mattered to them pertaining to their care experience. We then reviewed 12 measures of patient surveys to identify existing validated evaluation tools for patient experience. We critically examined these against core domains of the Cancer Life ReiMagined (CaLM) model of care: Whole Person Care, Care Coordination, Communication, Empowerment, Access to Care. Of 4 measures identified, 9 validated items were chosen and combined with team-generated items to produce an initial 19-question form of the Oncology Patient Experience Survey. Results: We held two 1-hour sessions with two groups of patient advocates to guide and narrow the survey from each dimension of the original scale. Overall response to the survey was positive, but results from these sessions prompted heavy modifications, including creation of a new section of the survey that re-classified ‘non-cancer needs’ as 7 distinct domains, and the addition of 3 open-ended questions. Conclusions: The end result was a complete 33-item Oncology Patient Experience Survey, ready for deployment. This methodology serves as a novel, low-cost and timely way to implement site-specific patient experience surveys without sacrificing quality.[Table: see text]
Elevated serum alpha-fetoprotein is a significant prognostic factor for gastric cancer patients: Results based on a large-scale retrospective study.
Authors: Zhouwei Zhan
Journal: Journal of Clinical Oncology (2022)

e16059 Background: To study the clinicopathological features and prognostic factors of serum alpha-fetoprotein (AFP) positive gastric cancer (GC). Methods: A cohort study including 2318 GC patients who underwent radical surgery from January 2008 to December 2015 was retrospectively analyzed. Patients were divided into two groups according to preoperative serum AFP values: 191 patients with AFP-positive GC (AFP &gt; 20ng/mL, 8.24%) and 2127 patients with AFP-negative GC (AFP≤20ng/mL, 91.76%). The clinicopathological features and prognostic factors were explored. Results: Compared with AFP-negative GC, AFP-positive GC had higher rates of liver metastasis, lymph node metastasis, venous invasion, and nerve invasion (all P&lt; 0.05). The 5-year OS, DFS and mLMFS of AFP-positive GC were shorter than AFP-negative GC (55.00% vs. 45.04%, P&lt; 0.001; 39.79% vs. 34.03%, P&lt; 0.001; 13.80 months vs. 16.25 months, P = 0.002). In whole cohort, multivariate analysis found serum AFP levels (positive vs negative), pT stage, pN stage, nerve invasion (yes or no), venous invasion (yes or no) were independent prognostic factors. Serum AFP levels (20-300 ng/mL vs. 300-1000 ng/mL vs. &gt; 1000 ng/mL), pT stage, pN stage, venous invasion (yes or no) were independent prognostic factors in AFP-positive GC. Conclusions: Liver metastases and venous invasion are more likely to occur in AFP-positive GC and lead to poor prognosis. Serum AFP level is an independent prognostic factor in GC patients. As the level of AFP increases, the prognosis becomes worse.
A controlled comparison of cerebral volume loss after brain irradiation with proton versus photon radiotherapy.
Authors: Melissa Gardner, Franziska Stahl, Jorg Dietrich, Elizabeth R. Gerstner, Janet Sherman, Helen Alice Shih, Michael Parsons
Journal: Journal of Clinical Oncology (2022)

2017 Background: Previous work has demonstrated cerebral volume loss after glioma treatment with concurrent photon radiotherapy (PHT) and chemotherapy. Proton radiotherapy (PRT) minimizes exposure of normal brain tissue compared with PHT. The objective of this study was to compare neurotoxic effects of PRT vs PHT in a retrospective case-matched control series of WHO grade 2 and 3 gliomas. Methods: PRT subjects were selected from ongoing longitudinal single-arm outcome studies being conducted at our institution (NCT01358058, NCT03286335). PHT subjects were identified via medical record search and were individually matched to PRT subjects using an eleven-tiered criterion (i.e., age, sex, tumor type, tumor location, laterality, IDH mutation status, 1p19q deletion status, concurrent chemotherapy, adjuvant chemotherapy, total Gy dose, and number of fractions). When individual matching was not possible on all 11 variables, efforts were made to identify the closest possible match. Only those subjects with at least two years of progression free survival and available T1 and T2/FLAIR MRI at baseline, one year, and two years following RT were included. The resulting sample included 17 PRT and 17 PHT patients with grade 2 and 3 gliomas (19 male; mean age = 40.10y; SD = 11.27). Non-parametric analyses were used to compare groups on demographic and tumor/treatment-related variables. Diffuse cerebral volume loss was estimated by manually measuring lateral ventricular volume in the tumor-free hemisphere. Results: Mann-Whitney tests of independence showed no significant differences between groups on any of the demographic variables or clinical characteristics. One-way ANOVA demonstrated that ventricular volume increase after two years was significantly greater in patients treated with PHT than with PRT, (F(1, 32.00) = 5.90, p &lt;.021, η 2 =.156). Change in ventricular volume in the PHT group was 24.85% (SD = 14.45%) and in the PRT group was 12.03% (SD = 16.3%). Conclusions: The findings of this study suggest that 2 years post treatment for glioma, PRT is associated with less brain volume loss and ventricular expansion than PHT. The findings support the hypothesis that PRT can reduce neurotoxicity within the tumor-free hemisphere. This study is limited by the retrospective design and lack of randomization to treatment arms, though cohorts were well-matched following a rigorous set of criteria. The effects of PRT beyond 2 years after treatment remain unknown. Preservation of brain structure may be critically important for maintenance of brain function in this population of patients who have prolonged survival. Longitudinal cognitive assessment in brain tumor patients undergoing PHT vs PRT is needed and is currently being collected in NRG BN-005 (NCT03180502), which may provide important data regarding functional impact of the brain changes we have demonstrated.
Complementary and alternative medicine use and recommendations for discontinuation of supplements in an integrative oncology clinic.
Authors: Stacy D. D'Andre, Brent D. Bauer, Maggie D. Hofmann, Jenna D. Burckhard, Heather D. Montane, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2022)

12058 Background: It is well established that many patients with cancer are taking dietary supplements (DS) and alternative medicines and often do not disclose such to their care teams. There is potential for harm in several ways: 1) interactions with their medications that may increase side effects, 2) interactions with their treatment that may lead to decreased efficacy, 3) direct toxicity from the supplement 4) financial toxicity. We have recently started a new Integrative Oncology service to help counsel patients about improving lifestyle factors and assist patients with safe and evidence-based integrative treatments and supplements. Methods: Patient data (N=100) were collected prospectively from an Integrative Oncology Clinic. The number and type of DS were documented. Using the Natural Medicines Database (NMD), we determined whether supplements interacted with the patients’ other medications or cancer therapies. We calculated the percentage of patients in which a recommendation for discontinuation of DS was recommended, along with the supporting reasons. We calculated the most common DS being taken and other alternative therapies beyond supplements. Results: Ninety-one percent of patients took DS, with an average of 5.5 per patient (range 0-20). The most common DS patients reported taking (%): Vit D (52), Vit C (41), Multivitamin (34), probiotic (27), B Vitamins (26), Ca (20), zinc (20), fish oil (18), cannabis (18), mushrooms (18), turmeric (17), magnesium (15), melatonin (14), biotin (11), coq10 (7), iron (8), VIT E (5), and glucosamine (5). Eighty-nine percent of patients using DS were on active cancer therapy. In thirty-five percent of patients, we recommended stopping some of their DS or other therapies. Number of patients using alternative therapies beyond DS: IV Vitamin C (5), Rick Simpson oil (high dose THC) (4), extreme diets (4), mistletoe (2), re-purposed meds (2); and one each was using hyperbaric O2, ozone, homeopathic, ayurvedic, insulin-potentiated chemo, miracle mineral cure, chelation, low dose naltrexone Conclusions: Cancer patients both on and off active treatment are using large numbers of DS with potential for adverse effects and/or decreasing efficacy of treatments. This study highlights the prevalence of DS and alternative medicine usage in cancer patients referred to an integrative oncology clinic and demonstrates the need for counseling about safe supplement use; in 35% of patients, discontinuation of DS was recommended. [Table: see text]
A novel humanized antibody targeting CD39 that enhances anti-tumor immunity and the efficacy of cancer immunotherapy.
Authors: Haruka Ban, Toshifumi Obonai, Yuji Mishima, Noriko Matsumoto, Motoya Mie, Norihiro Nakamura
Journal: Journal of Clinical Oncology (2022)

e14508 Background: Immunotherapy using immune-checkpoint inhibitors (ICIs) has shown remarkable clinical efficacy in patients with cancer. However, it is crucial to utilize appropriate combination of immunotherapy for patient condition, as most patients do not benefit or sustain responses of immunotherapy. We focused on CD39 that is highly expressed in some tumors and tumor infiltrating immune cells (e.g. exhausted T cells and Tregs) as a target for cancer immunotherapy. CD39 is an ectoenzyme that converts extracellular ATP to immunosuppressive adenosine. Since the ATP-adenosine pathway is a key modulator of innate and adaptive immunity within the tumor microenvironment (TME), we presume that anti-CD39 antibodies suppress the production of adenosine and limit the immunosuppressive state in TMEs. Methods: Anti-human CD39 antibodies were screened by sorting B cells of mice immunized with human CD39 protein. The obtained clones that inhibit enzyme activity of CD39 were humanized on IgG1 and IgG4. PBMC were used in proliferation and functional assays. The anti-tumor effect was investigated with mouse xenograft model. Results: Analyzing gene expression profiles from TCGA data, high CD39 expression is associated with a poor prognosis in several cancers. There was a strong correlation between them in multiple myeloma treated with chemotherapies. The expression of CD39 was upregulated in some cancer cell lines treated with chemotherapeutic agents. A novel humanized anti-CD39 antibody, BP1202, which has a high affinity for the recombinant CD39 protein (K D : 481 pM) and inhibits the enzyme activity of CD39 expressed on a cancer cell line (IC 50 : 1 nM) and human Tregs. The antibody showed a high potency to enhance T cell activity including their proliferation, cytokine production, and cytotoxicity against a cancer cell line. We examined the anti-tumor effect of BP1202 in vivo using tumor-bearing mice and found that the combination treatment of BP1202 with chemotherapeutic agents significantly reduced tumor volume. Conclusions: We developed a new humanized antibody that enhances anti-tumor immunity by inhibiting CD39 expressed on exhausted T cells and intra-tumor T cells. These data suggest the scientific rationale for the clinical development of BP1202 and their use in combination with ICIs, with ATP-adenosine pathway inhibitors, and with chemotherapies. BP1202 is currently being developed as a new antibody agent for cancer immunotherapy.